posted on 2000-05-27, 00:00authored byChristopher J. La Francois, Yun Hee Jang, Tahir Cagin, William A. Goddard, Lawrence C. Sowers
Emerging data strongly suggest that the oxidation of DNA bases can contribute to genomic
instability. Structural changes to DNA, induced by base oxidation, may reduce the fidelity of
DNA replication and interfere with sequence-specific DNA−protein interactions. We have
examined the structures of a series of pyrimidine deoxynucleoside oxidation damage products
in aqueous solution. The modified nucleosides studied include the deoxynucleoside derivatives
of 5-hydroxyuracil, 5-hydroxycytosine, 5-(hydroxymethyl)uracil, 5-(hydroxymethyl)cytosine,
5-formyluracil, and 5-formylcytosine. The influence of base oxidation on ionization constants,
sugar conformation, and tautomeric configuration has been determined on the basis of UV,
proton, and nitrogen NMR spectra of the 15N-enriched derivatives. The potential biological
consequences of the structural perturbations resulting from base oxidation are discussed.